Cross-linked acrylic acid polymer admixed with polyethylene glycol



3,461,089 CROSS-LINKED ACRYLIC ACID POLYMER AD- MHXED WilTH POLYETHYLENEGLYCOL Normand E. Erindamour, Worcester, Pa, assignor to Merck d; (10.,ilnc., Rahway, N..l., a corporation of New Jersey No Drawing. Uriginalapplication Apr. 21, 1964, Ser. No. 361,537, now Patent No. 3,379,554.Divided and this application Nov. 6, 1967, Ser. No. 704,194

lint. Cl. (308E 37/00, 45/34 11$. Cl. 260-114 2 Claims ABSTRACT OF THEDISCLOSURE Coatings for tablets and other individual solid medicinaldosage forms are disclosed comprising a water-soluble acrylic acidpolymer cross-linked with polyallyl sucrose and admixed withpolyethylene glycol.

This invention relates to novel compositions of coatings for tablets andother individual solid medicinal dosage forms which are characterized bya thin film outer layer of a Water dispersible or water solublecomposition. The invention also involves a novel spray method ofapplication of the composition.

This application is a division of my application Ser. No. 361,537, filedApr. 21, 1964, now Patent 3,379,554.

This invention provides an improved series of coating compositions basedon the combined use of known film forming materials. One ingredient ischosen from a group (1) high molecular weight polyethyleneglycols andtheir esters and the other ingredient is chosen from a group of (2) highmolecular weight carboxyvinyl polymers. The resulting coating has thefollowing particular advantages:

(1) The vinyl polymer imparts water solubility to the coating.

(2) The vinyl polymer is used in smaller amounts than if it were usedalone.

Although the (1) polyethylene glycols and their esters and the (2)carboxylvinyl polymers have been employed in making tablets and tabletcoatings, the first as a film and the second to delay release, theircombination in accordance with this invention produces an unexpectedlyvaluable coating. Neither (1) or (2) can be applied alone to a core toprovide a satisfactory coating having the required pharmaceuticalrequisites. The first when used alone produces too soft a coat, is notsmooth, has an orange peel effect, and has a low melting point. Thesecond cannot be poured by itself to give satisfactory coatings nor canit be sprayed without forming cobwebs. Modifying (2) and (l) andapplying the combination of this novel process produces a continuousfilm which is hard, glossy and smooth, will not chip, and can be made tohave the required pearlescence.

The carboxyvinyl polymers are described in the data bulletin, Carbopol934, B. F. Goodrich Chemical Company and also in Chem. Eng. News, 36,No. 39, p. 64, Sept. 29, 1958. The preferred polymer is sold as Carbopol934, but it may be any one of the water soluble vinyl polymers havingactive carboxy groups as is disclosed in United States Patent No.2,909,462. The polyethylene glycols useful for the present invention aresolids having the formula -HOCH (CH OCH ),,CH OH in which n is a wholenumber which will give a molecular weight of from 3,000 to 20,000.Suitable ones are sold under the trademark Carbowax. Their esters areformed with fatty acids.

It has now been found that a continuous, non-toxic, glossy film coatinghaving that required solubility characteristics may be produced onshaped cores containing 3,461,089 Patented Aug. 12, 1000 icepharmaceutical ingredients by the deposition thereon of a compositionconsisting essentially of a solution of 5 to 10 parts by weight of (1)the polyethylene glycol and 1 part by weight of (2) the water solublecarboxyvinyl polymer, minor amounts of gelling, suspending, opacitying,plasticizing, solubilizing, coloring, glossing, tack reducing, andalkalizing agents of the kinds commonly used in pharmaceuticalmanufacture may or may not be used.

Solvents suitable for the process may be water, methanol, ethanol,isopropanol, propanol, acetone, methyl ethyl ketone, chloroform,methylene chloride, carbon tetrachloride, chloroethene,dimethylacetamide, methyl acetate, ethyl acetate, ethyl lactate,dioxane, benzene, toluene, Freona (the groups of low boiling alcohols),aldehydes and ketones, and mixtures or blends of the above. Theseingredients may be used in the following ranges in making up the liquidcomposition to be applied to the tablet to form a film coating therein:

Percent Carboxyvinyl polymer 0.01 to 3 Polyethylene glycol 4,000 to20,000 0.05 to 30 In using this composition it is possible to use aconventional pear shaped rotating coating pan and to spray it on thetumbling tablets. However, best results are obtained if one uses thespecially designed rotating coating pan and its associated equipmentwhich are described in my patent application Ser. No. 347,804 filed onApr. 6, 1964. That description is incorporated herein by reference.

The following examples are presented in order to describe the inventionmore fully, but it should be understood that the invention is notintended in any way to be limited by the examples.

EXAMPLE 1 Coating solution Two grams of Carbopol 934 and 20 grams ofCarbowax 6000 were dissolved in enough methanol to make ml.

Coating procedure Five hundred grams of standard curvature placebotablets each weighing 270 mg. were placed in the coating pan equippedwith a blower to direct dry air on the tumbling tablets and with anexhaust system to suck air from the interior of the pan. A paintcontainer and spray nozzle operated at 30 pounds air pressure and havinga 10" fluid head pressure was placed to continuously coat the tumblingtablets. The coating pan was rotated at 30 rpm. The solution was sprayedin such a direction that the plane of the tablet flow surface formed aright angle with the line of spray, the spray distance to the tabletsbeing 3". The drying air input and exhaust were acljusted to prevent thetablet load from becoming wet as the film was deposited on theindividual tablets. The temperature of the tablet bed was kept within 20and 30 C. The solution was sprayed at the rate of 5 ml. per minute until100 ml. had been consumed. The tablets were allowed to roll for 15minutes after the final application of the solution. The resultingtablets were glossy, smooth, and homogeneously coated. Thedisintegration time of both the coated and uncoated tablet was the same.A gas chromatogram of the coated tablet showed no residual solvent. Thecoating is not softened when exposed to either 50 C. or to a 75%relative humidity atmosphere for a period of two weeks.

EXAMPLE 2 The coating of Example 1 was carried out except that ironoxide was suspended in the film coating solution, and Carbowax 4000 wassubstituted for the Carbowax 6000.

EXAMPLE 3 A 500 gram batch of A" standard curvature amitriptyline (soldunder the trademark Elavil) tablets was coated with a solutioncontaining 0.5% Carbopol 934 and 5% Carbowax 6000 so that the initial270 mg. tablet was coated with 2.88 mg. of solids. The 30-40 minutesdisintegration time was unchanged after the addition of the film.

EXAMPLE 4 The coating of Example 3 was carried out except that 5% ironoxide was suspended in the film coating solution, and polyethyleneglycol having an average molecular weight of 20,000 was substituted forthe Carbowax 6000.

EXAMPLE 5 A 500 gram batch of capsule-shaped tablets containingdexamethasone and aspirin (solid under the trademark Decagesi c) wascoated with a solution containing 0.5% Carbopol 934 and 2.5% Carbowax6000 in methanol so that the initial 700 mg. tablet was coated with 6mg. of solids. The uncoated disintegration time of 4 to 5 minutes wasunaffected by the coating.

EXAMPLE 6 The coating of Example 5 was carried out except that the spraywas stopped after each ml. of solution and the damp tablets were dustedwith yellow talc in such a manner that each tablet was coated with 30mg. of yellow talc for a total 36 mg. of solids. The uncoateddisintegration time of 4 to 5 minutes was unaffected by the coating. Thetalc imparts a pearly sheen to the tablets.

EXAMPLE 7 A 500 gram batch of A" standard curvature amitriptylinetablets (solid under the trademark Elavil) was coated with a solutioncontaining 0.5 Carbopol 934 and 2.5 Carbowax 6000 in methanol so thatthe initial 120 mg. tablet was coated with 1.44 mg. of solids. The 30 to40 minute disintegration time of the uncoated tablet was unaffected bythe coating.

EXAMPLE 8 The coating of Example 7 was carried out except that the spraywas stopped after each 5 ml. of solution and the damp tablets weredusted with yellow talc in such a manner that each tablet was coatedwith 5 mg. of yellow tale for a total 6.44 mg. of solids. The 30 to 40minute disintegration time of the uncoated tablet was unafiected by thecoating. The talc imparted a pearly sheen to the tablets.

EXAMPLE 9 A 500 gram batch of standard curvature indomethacin tablets(sold under the trademark Indocin) engraved with a symbol was coatedwith a solution containing 0.5% Carbopol 934 and 2.5% Carbowax 6000 inmethanol so that the initial 200 mg. tablet was coated with 2.4 mg. ofsolids. The 3 to 5 minute disintegration time of the uncoated tablet wasunchanged by the coating. The symbol was clear.

4 EXAMPLE 10 The coating of Example 9 was carried out except that thespray Was stopped after each 10 ml. of solution and the damp tabletswere dusted with a blend of talc, iron oxide, and titanium dioxide insuch a manner that each tablet was coated with 8.8 mg. of talc, 1 mg. ofiron oxide, and 0.2 mg. of titanium dioxide for a total 12.4 mg. ofsolids. The 3 to 5 minute disintegration time of the uncoated tablet wasunaffected by the coating. The symbol was coated and clear. The tabletsacquired a pearly sheen.

EXAMPLE 1 l A 500 gram batch of A" standard curvature Elavil tablets wascoated with a solution of 2% Carbopol 934 and 20% Carbowax 6000 in waterso that the initial mg. tablet was coated with 10.08 mg. of solids. Thespray was stopped after each 5 m1. of solution and the damp tablets weredusted with yellow talc. The 30 to 40 minute disintegration time of theuncoated tablet was unalfected by the coating.

EXAMPLE 12 The polyethylene glycol used in any one of the above examplesmay be replaced with the known corresponding fatty acid ester. Forinstance, the Carbowax 6000 used in Example 11 may be replaced withpolyethylene glycol 6000 monostearate.

In the appended claims, reference to polyethylene glycol is intended toinclude both the free alcohol and the fatty acid esters.

What is claimed is:

1. The film coating comprised of (A) one part by weight of awater-soluble polymer of acrylic acid crosslinked with approximately 1%of polyallyl sucrose and having an approximate molecular weight of200,000 and (B) from 5 to 10 parts by weight of a polyethylene glycolhaving an average molecular weight of from about 3,000 to 20,000.

2. A liquid composition for applying a film coating to a medicinal core,which has the following ingredients:

Percent Water-soluble polymer of acrylic acid crosslinked withapproximately 1% of polyallyl sucrose, M.W. approx. 200,000 0.01 to 3Polyethylene glycol 4,000 to 20,000 0.05 to 30 Gelling, tack reducing,suspending agent 0 to 5 Opacifying agent 0 to 10 Tack reducing, glossingagent 0 to 20 Organic or inorganic alkalizing agent 0 to 10 Plasticizingagent 0 to 5 Surfactant 0 to 0.5 Coloring agent 0 to 5 Solvent Q.s.

References Cited UNITED STATES PATENTS 3,149,041 9/ 1964 Jeifries260-332 X 3,206,420 9/ 1965- Smart et al. 260-33.2 X 3,361,702 1/1968Wartman et a1. 260-332 MORRIS LIEBMAN, Primary Examiner L. T. JACOBS,Assistant Examiner US. Cl. X.R. 26028, 33

